The application of siRNA to medical treatments is increasingly expected because the siRNA can knock down target mRNA specifically and effectively. However, the development of an effective delivery system is indispensable to apply the siRNA to medical treatments. In recent years, it has been clarified that an therapeutic effect of naked siRNA on age-related macular degeneration (CNV) through its intraocular administration under a clinical trial does not result from a sequence-specific gene knockdown effect induced by siRNA but results from a non-sequence-specific effect via recognition by Toll-like receptor-3 (TLR-3) on cell surface. It has been considered important to develop a carrier that is stable outside cells and is capable of accurately delivering siRNA into the cells in any of in vivo siRNA applications.
Hitherto, a variety of cationic polymers have been provided as carriers for forming a polyion complex (PIC) with DNA and introducing and expressing the nucleic acid in eukaryotic cells. For example, it is known that a poly(L-lysine) derivative in which a hydrophilic group (e.g., polyethylene glycol) and a hydrophobic group (e.g., a palmitoyl group) have been introduced via an ε-amino group of poly(L-lysine) forms a vesicle in the presence of cholesterol in an aqueous medium and the vesicle aggregates gene-containing plasmid DNA to form a stable complex (Patent Document 1). Further, a PIC formed of plasmid DNA with a copolymer derivative whose cation charge and disulfide crosslink density have been adjusted by the thiolation of an ε-amino group of poly(L-lysine) in a poly(L-lysine)-poly(ethylene glycol) copolymer is known to show high stability in an extracellular medium and effectively release the DNA in an intracellular compartment (Non Patent Document 1). Further, it has been confirmed that, when poly(N-[N-(2-aminoethyl)-2-aminoethyl]aspartamide (pAsp (DET))) having an ethylenediamine structure in a side chain and a block copolymer including the pAsp (DET) as one of block components of the block copolymer are produced, such polymers show low cytotoxicity and introduce plasmid DNA into cells with high efficiency to express a gene incorporated into the DNA efficiently (see Non Patent Document 2, Patent Document 2, and Patent Document 3).
As described above, although a carrier effective for a high molecular weight nucleic acid such as DNA has been developed, a carrier capable of forming a stable complex such as a PIC with a low molecular weight nucleic acid such as siRNA as well under a physiological condition and suitably releasing the low molecular weight nucleic acid in cells has not been provided yet.